The present invention relates generally to devices and methods for performing microbeam radiation therapy on a subject for treatment of tumors and of other diseases, and more particularly to a stereotactic device and method of delivering microbeam arrays from multiple angular directions to produce a broad beam effect only within a target volume thus increasing the therapeutic effect of microbeam radiation therapy.
Cancer continues to be one of the foremost health problems. Conventional treatments such as surgery, chemotherapy and radiation therapy have exhibited favorable results in many cases, while failing to be completely satisfactory and effective in all instances. For example, the effectiveness of orthodox radiation therapy on deep pulmonary, bronchial, and esophageal tumors is limited by the risk of radiation pneumonitis. Also, non-tumor applications of radiation therapy, such as the ablation of epileptogenic foci, are still considered a challenge with conventional radiation therapy and radiosurgery.
The goal of radiation therapy is generally to maximize the therapeutic index, which is defined as the ratio of the maximum tolerable dose beyond which unacceptable levels of normal tissue toxicity would occur, to the minimal dose required for effective tumor control. This goal is particularly difficult to achieve in treating central nervous system (CNS) tumors. Malignant gliomas which include astrocytomas, oligodendrogliomas and glioblastoma represent about 60% of all primary brain tumors, with an incidence of over 8,000 cases per year. The survival statistics of patients with high grade gliomas in the brain, or lower grade gliomas and metastatic tumors in the spinal cord have not improved appreciably in recent years using conventional surgical techniques and conventional radiotherapy. The doses that can be delivered to malignant CNS tumors are limited by the tolerance of normal brain and spinal cord to radiation. For higher grade CNS tumors, radiation is generally offered only as a palliative rather than curative therapy. For lower grade CNS tumors, the ratio of radiotherapy doses that produce normal CNS toxicity and those that control the tumor is so close that it often renders radiotherapy ineffective, or results in neurological complications from radiotoxicity to the normal CNS surrounding the tumor. In addition, tolerance of the normal CNS to re-treatment, if necessary, will be lower.
Conventional radiation therapy has serious limitations due to radiation damage to normal tissues. Although stereotactic radiosurgery has improved the outcomes, highly radiosensitive structures located in the vicinity of the target remain a limiting factor. It is well known to those skilled in the art that the threshold dose, or maximum tolerable dose before neurological and other complications of radiotherapy arise, increases as irradiated volumes of tissue are made smaller. Such observations eventually led to the development of grid radiotherapy using grids or sieves for spatial fractionation of X-rays.
Recently, a much less familiar alternative form of radiation therapy, known as microbeam radiation therapy (MRT), has been investigated in laboratory animals to treat tumors such as those for which the conventional methods are ineffective or associated with a high risk factor. The concept of MRT was introduced in U.S. Pat. No. 5,339,347 to Slatkin et al. MRT differs from conventional radiation therapy by employing arrays of parallel planes of radiation, which are at least one order of magnitude smaller in thickness (or diameter if, in the rare case, parallel cylindrical beams are used rather than planar beams) than the smallest radiation beams in current conventional clinical use. These very thin microbeams, which are also called microplanar beams, can be generated using the high intensity X-ray beams that are currently generated at electron synchrotron storage rings.
There are three disadvantages of the broad beams currently used in clinical radiation therapy over microbeams. First, they do not allow treatment of very small targets (because of their size limit), and they give additional dose to the neighboring non-targeted tissue (because of their un-sharp edges). Second, they will not have the tissue-sparing effect of x-ray microbeams (or microplanar beams) that are possessed only by sub-millimeter or millimeter beams. Third, they are usually administered in many dose fractions, which is often difficult on the patent.
The Slatkin et al. patent discloses the segmentation of a broad beam of high energy X-ray into arrays of parallel microbeams (beams of thickness less than about 1 millimeter (mm)), and a method of using the microbeams to perform radiation therapy. The target tissue, e.g., a tumor, receives a summed absorbed dose of radiation exceeding a maximum absorbed dose tolerable by the target tissue by crossing or intersecting the microbeam arrays at the target tissue. The irradiated in-path non-target tissue is exposed only to non-crossing beams. Non-target tissue between the microbeams receives a summed absorbed dose of radiation less than the maximum tolerable dose, i.e., a non-lethal dose to non-target tissue. In this way, the irradiated non-target tissue in the path of the microbeam is allowed to recover from any radiation injury by regeneration from the supportive cells surviving between microbeams. The probability of radiation-induced coagulative necrosis in the irradiated normal, non-targeted tissue is also lowered due to the non-crossing beam geometry in the non-target tissue, allowing for lower levels of radiation to the non-target tissue. Using microbeam radiation therapy in this way helps improve the effectiveness of clinical radiation therapy, especially for deep-seated tumors. Finally, it was shown that microbeams have a “preferential tumoricidal effect”, i.e., they damage the tumor preferentially while sparing the surrounding normal tissues. This effect, observed in tumor-bearing rats and mice irradiated with microbeam, arrays from a single direction, has an important implication on the present patent.
The microbeams geometries disclosed in the Slatkin et al. patent are of two basic types. Exposure of the target may be accomplished by a unidirectional array of microbeams which may be parallel or may converge at the target. Alternatively, two arrays of microbeams originating from different directions may be “cross-fired,” and intersect at an isocenter in the target tissue. The microbeams within each array may be substantially parallel to each other or may converge at an isocenter within the target.
Commonly owned U.S. Pat. Nos. 7,158,607 and 7,194,063 to Dilmanian, the specifications of which are incorporated herein by reference, disclose improvements on the MRT method disclosed in the Slatkin et al. patent. In U.S. Pat. No. 7,158,607, two arrays of microbeams are interlaced or interleaved at a target tissue to produce a continuous broad beam effect only within the target volume. In U.S. Pat. No. 7,194,063, a method of administration of microplanar beam arrays was shown that was particularly useful for assisting recovery of a damaged spinal cord and a brain.
An important concept in microbeam radiation therapy is the “valley dose”. It is the radiation leakage between the beams caused mostly by x-ray scattering. For the normal tissues surrounding the target to be spared from the radiation, the valley dose in the normal tissue should be adequately low to allow the supportive cells to survive.
There is a need in the prior art for further improvements of radiation therapy, as well as efficient devices for implementing MRT, which greatly enhance the therapeutic dose at a target, while simultaneously maintaining a safe dose to normal tissue. There is also a need, which is lacking in the prior art, for an effective system to perform multiple-angle delivery of microbeams simply on tissues affected by diseases and conditions without inducing radiation injury to surrounding healthy tissue.